Elsevier

Journal of Chromatography B

Volume 900, 1 July 2012, Pages 89-93
Journal of Chromatography B

Short Communication
A liquid chromatography–tandem mass spectrometric method for quantification of curcumin-O-glucuronide and curcumin in human plasma

https://doi.org/10.1016/j.jchromb.2012.05.026Get rights and content

Abstract

Curcumin is a widely used herbal medicine for various human diseases including inflammation and cancer. The demonstration and optimization of curcumin's activities in the clinical setting, however, have been compromised by its poor bioavailability and the lack of analytic methods to monitor its absorption. In this paper, we report the first validated liquid chromatography–tandem mass spectrometric method for simultaneous quantification of curcumin and its major metabolite: curcumin-O-glucuronide (COG), in the linear range of 2.0–2000 ng/mL in human plasma. The intra-day and inter-day accuracies of curcumin and COG in human plasma were in the range of 91.3–111.5% and 82.7–109.2% and their co-efficiency of variations were in the range of 3.5–12.7% and 3.1–11.3%, respectively. This method was capable of detecting only COG in human plasma samples from two healthy volunteers after an oral ingestion of curcumin.

Highlights

► First direct method to measure curcumin-O-glucuronide (COG) in human plasma. ► The LLOQ is 2 ng/mL with CVs (<15%) and accuracy (85–115%). ► Capable of characterizing the pharmacokinetics of COG up to 24 h in human.

Introduction

Curcumin is a natural polyphenol extracted from the rhizome of turmeric (Curcuma longa) [1], [2]. Curcumin possesses a wide range of biological and pharmacological activities including anti-oxidant, anti-inflammatory and anti-tumor effects, most of which have been elucidated from preclinical studies [3]. Due to the lack of analytic methods to monitor its absorption, current application of curcumin in clinical setting has not been optimized [4]. Pharmacokinetic (PK) studies of curcumin in humans have consistently reported low plasma curcumin levels (<50 ng/mL) after oral ingestion of curcumin up to 12 g/day [5], [6]. Factors contributing to its low oral bioavailability include its poor solubility and absorption, and rapid metabolism [4]. Metabolic studies have demonstrated that orally ingested curcumin is extensively transformed to curcumin-O-glucuronide (COG) and curcumin-O-sulfate (COS) in both rodents [7], [8] and human [6]. As the major metabolite, COG may be explored as a potential marker for evaluating curcumin absorption and monitoring the compliance of curcumin consumption. Up to date, the plasma level of COG has been determined indirectly by quantifying curcumin generated from glucuronidase hydrolysis of plasma samples [6]. In this study, a sensitive LC–MS/MS method for direct quantification of COG and curcumin has been established and validated in human plasma.

Section snippets

Reagents and chemicals

Curcumin (>98%) was purchased from Acros Organics (Acros Organics, Morris Plains, NJ) and used for developing a calibration curve without further purification. Curcumin-O-glucuronide (COG) was custom-synthesized from Cell Mosaic (Worcester, MA). Curcumin C3 complex (CC3C) was purchased as a dietary supplement from Ageless Inc. (Ann Arbor, MI). The internal standard (I.S.), hesperetin, was obtained as a white powder from the National Cancer Institute (NCI) and used without further purification.

Mass spectrometric characterization of curcumin and COG

The chemical authenticity and mass and tandem mass spectra of curcumin have been reported [9]. Chemical authenticity of COG was confirmed on a TSQ quantum triple quadruple mass spectrometer. Under a positive ion mode, standard solutions of 10 μg/mL COG in 50% acetonitrile containing 0.1% formic acid were infused with an LC flow of 0.2 mL/min into a TSQ mass spectrometer electro-spray ion (ESI) source. The full scan mass spectrum (Fig. 1A) of COG showed a predominant ion at m/z 545, corresponding

Conclusions

An LC–MS/MS method for direct quantification of COG and curcumin was developed in human plasma and this method is capable of detecting COG in human plasma up to 24 h after an oral administration of 4 g curcumin as curcumin C3 complex. This direct method is more efficient in COG quantification when compared with currently used indirect methods through avoiding repeat sampling and analysis, and the pretreatment of the biological matrices with β-glucuronidase. Therefore, this method provided a

Acknowledgments

This work was supported by National Institute of Health (NIH) grants [R21 CA135478], the National Center for Research Resources [UL1RR025755] and Biomedical Mass Spectrometric Laboratory at The Ohio State University.

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